When the pharmaceutical industry started to research vaccines to fight COVID-19 in the spring of 2020, the concern that global manufacturing and packaging capacities would need to be increased arose almost simultaneously. At Catalent Pharma Solutions, a leading development and manufacturing partner to pharmaceutical companies, preparations began to boost vaccine production capabilities. As a part of this preparation Optima accelerated a program to make new Optima filling and closing machines, with isolators, ready to start almost at the push of a button as soon as emergency use authorizations were granted.
Catalent works closely with its customers to manufacture life-enhancing and life-saving medicines, including COVID-19 treatments and vaccines. Prior to the pandemic, Catalent had announced an expansion at its facility in Bloomington, Indiana, to meet customer demand and the projected growth of fill/finish within the industry.
It quickly became apparent that an unprecedented number of treatments and vaccines would be needed to fight COVID-19, so Catalent accelerated its expansion to bring additional capacities online sooner.
At Catalent, the OPTIMA VFVM 18000 filling and closing machine is used. The complete filling line handles washing, sterilizing, filling and closing of vials under isolator
The new vial filling line orders from Catalent enabled Optima to contribute to expanding global vial capacities. Typically, projects of this magnitude could take years until production can begin, however, both vial lines were accelerated to meet Catalent’s customers’ demand of biologics, including COVID-19 vaccines.
Prior to the pandemic, Catalent had already announced an expansion to add capacity in Bloomington, and had ordered a vial line from Optima. This pre-planned vial line turned out to be a very good option for vaccine production. Nonetheless, the technical concept still had to be modified in record time to meet the requirements of Catalent’s customer’s new product, and without compromise. For Catalent’s second vial line, it was possible to transfer another Optima line, but again with the same time restrictions and a new, specific line design.
Now, Optima and Catalent, who share a long-standing relationship, were being challenged to make the impossible happen. The first requirement for the systems was a new Catalent building. Here, Catalent expedited its own planning and construction to bring the program forward by ten months. At Optima, both lines were given priority.
Plant planning and vaccine development were running in parallel, so a certain degree of flexibility in the technical design of the line was initially required. Rebecca Mullis, Lead Process Engineer at Catalent Biologics, commented, "The output of the line is very important. Catalent wanted a high-speed line to bring life-saving medicines to market safely, and as quickly as possible.”
Output was designed at up to 24,000 vials per hour, which can be achieved with 2R vials and ten-digit processing. The second line dispenses at a rate of up to 16,200 vials per hour into 10R vials. At the same time, high filling accuracy had to be achieved. Both lines were to operate with 100% in-process control and were to be equipped with Optima's isolator technology.
High speed, precision filling: Up to 24,000 vials per hour are processed by the system. 100 percent of the containers are inspected by an in-process control.
Vials filled with vaccines and tested are lined up and compactly grouped with a tray loader.
One of the world's largest cargo aircraft, the Antonov An-124, is being loaded.
The turnkey plant engineering used by Optima Pharma meant that Catalent was able to enjoy a single point of contact for the entire solution. Both lines subsequently benefited from the fact that the isolator, filling, and closing machines were fundamentally aligned, from the mechanical fits to Environmental Monitoring System systems (EMS*) to the electronics and controls. Outwardly, this can best be seen in the software integration of the isolator into the machine control system - all parts of the system are operated via a central Human-Machine Interface (HMI). This greatly reduces potential sources of error, which, along with simplified project organization, yields considerable time benefits.
Comprehensive Scientific Process Engineering (CSPE) is another process employed by Optima Pharma. CSPE has made it possible to perform advanced virtual testing of the interfaces between the isolator, the filling, and the closing machine across different locations. In the CSPE center, both lines were set up complete with isolator. The high complexity of such systems means that, even in a turnkey project, it makes sense to test the entire unit as comprehensively as possible for the Factory Acceptance Test (FAT), so that massive time savings can be achieved once installed at a customer's own premises.
In addition, Optima Pharma has a library of software modules that also function as a programing standard. These tried and tested modules were able to be used for many of the functions of both lines, and this also saved time; software development and configuration was done simultaneously with the system design. .
Finally, there were also some very practical things that facilitated rapid implementation. "Optima has shown very high commitment to helping Catalent,” says Mullis. She added, “We were assisted in the fast-track of both projects, and Optima provided all the resources needed to do so, enabling us to meet the extremely tight schedule. There were frequent conference calls scheduled overnight, so that we could initiate a dialogue with the experts the very next day."
At the same time as the equipment was being built, Optima was already working on logistics. In early August, part of the first line was shipped to the U.S. by sea. Then, at the end of August, one of the world's largest cargo aircrafts, an Antonov An-124, took off from Europe bound for the U.S. On board: 38 tons of high-tech system modules, which would have previously been transported using several heavy-duty trucks from the Schwaebisch Hall and Radolfzell sites (isolator technology) to an European cargo airport. In the time gained by air freighting, the filling machine and the isolator were fully completed.
All the components arrived at Catalent together and on time to the very day. These special shipping channels also made it possible to speed up the re-commissioning process, i.e., the reassembly of the plant at the customer's site using as few components as possible.
EMS stands for Environmental Monitoring Systems. Multiple parameters are measured and assessed in the isolator-protected machine. Specifically, these include particle counters for air quality, germ collectors, and sensors for air temperature and humidity.
„Catalent wanted a highspeed line to have a life-saving
medications to market as safely and quickly as possible.“
"Optima manufactures quality equipment that has precision built into all of its parts and systems, and is precisely engineered. Even the 3D models show a high level of detail with which Optima achieves high precision and reproducibility. This makes it possible to build high-quality lines right from the get-go," says Mullis. Software parameters from similar projects that had already been implemented also helped to quickly breathe life into the system functions during the commissioning of this new vial line.
The first site acceptance test (SAT) was conducted at the Catalent site in the fall of 2020. Since the system installation began, Optima’s experts in Green Bay, U.S. were on hand to assist its customer. Work was carried out in two shifts and during weekends, based on COVID-19 health and safety protocols in order to maximize the (working) time available.
The first engineering runs to fine-tune the system were performed at the end of 2020. Even the isolator cycle development benefited from turnkey system integration and prior experience. The DECOpulse® decontamination system was set up and the cycle development was completed within weeks. Catalent then performed the process qualification. In close cooperation with the authorities and in compliance with all regulations, Catalent was able to include several values which were obtained and collected by Optima during the project phase as a reference. With this approach, the process qualification could be accelerated.
Optima succeeded in hugely expediting both vial line projects. But it was not just the scheduled deadlines that were met. Much more importantly, the work resulted in equipment and processing that met the extremely high quality standards of the pharmaceutical industry and Catalent. Close, trusting cooperation between the parties was a precondition for this success.
Catalent's second line at Optima Pharma's CSPE Center: There is adequate space for the air handling units.
Assembly of the CG membrane. The filling machine and the isolator are tested together in the subsequent integrated Factory Acceptance Test (iFAT).
As Catalent began manufacturing vaccines on its new vial line, the fight to respond to the COVID-19 pandemic continued with line two. An integrated FAT of the second filling machine with isolator was carried out in the fall of 2020, followed by SAT in the beginning of 2021, and production commencing shortly after. Catalent has also processed vaccines and treatments to protect against COVID-19 using pre-existing Optima equipment. The flexibility of formats and filling systems are integral parts of the design concept.
Like everyone involved at Optima and Catalent, David Di Palo, Optima's project manager, worked very hard over a period of months; his conclusion is remarkable: "The issue of COVID-19 affects us all, and I am definitely proud to be part of a project that is helping to bring a vaccine to market that will help people all over the world."
The significance of these efforts made by Catalent and all industry partners was made clear, in particular by a visit from former U.S. Vice President Mike Pence, who visited the Bloomington site on December 15, 2020, where he viewed manufacturing and packaging operations at the site.